Suppression of Th1 and Th17, but not Th2, responses in a CD8(+) T cell-mediated model of oral tolerance

Mucosal Immunol. 2009 Sep;2(5):427-38. doi: 10.1038/mi.2009.93. Epub 2009 Jul 1.

Abstract

The role of CD8(+) T cells in oral tolerance remains unclear. To address this, we developed a model to induce CD8(+) Tregs by feeding the major histocompatibility complex class I immunodominant epitope of OVA, OVA((257-264)). OVA((257-264)) feeding induced tolerance similar to that observed in OVA protein-fed mice, capable of suppressing the production of Th1 and Th17 cytokines and inhibiting a Th1-driven delayed-type hypersensitivity response following immunization with whole OVA (wOVA) protein. OVA((257-264)) peptide-induced suppression could be transferred to naive mice with CD8(+) cells, but not CD8-depleted cells, isolated from mesenteric lymph nodes of peptide-fed mice. Interestingly, while capable of inhibiting Th1 and Th17 responses, OVA((257-264)) feeding could not suppress any feature of a Th2 inflammatory response, though OVA protein feeding could, suggesting that these cells function through a different mechanism than their CD4(+) counterparts generated in response to feeding with wOVA. Thus, CD8(+) T cells are functionally capable of mediating tolerance to Th1 and Th17 responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Administration, Oral
  • Adoptive Transfer
  • Alveolitis, Extrinsic Allergic / immunology
  • Alveolitis, Extrinsic Allergic / pathology
  • Alveolitis, Extrinsic Allergic / prevention & control*
  • Animals
  • Antigens / administration & dosage*
  • Antigens / immunology
  • Antigens / toxicity
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Desensitization, Immunologic / methods*
  • Ear, External / immunology
  • Ear, External / pathology
  • Edema / etiology
  • Edema / immunology
  • Edema / pathology
  • Immune Tolerance / immunology*
  • Immunization
  • Immunodominant Epitopes / administration & dosage*
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / toxicity
  • Injections, Intradermal
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Ovalbumin / toxicity
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Peptide Fragments / toxicity
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antigens
  • Immunodominant Epitopes
  • OVA-8
  • Peptide Fragments
  • Ovalbumin